Apparatus and method for separation of particles suspended in a liquid from the liquid in which they are suspended

Abstract

A method for separating, or removing, particulate material, e.g., blood cells, from a sample of fluid, e.g., whole blood of a patient, in which the particulate material is suspended. In the case of separating blood cells from blood plasma or blood serum, the resulting samples of blood plasma or blood serum can be used for in vitro diagnostic applications. In normal practice, a whole blood sample of a patient are provided and then introduced into an apparatus that contains a flow channel. An acoustic field, which contains acoustic standing waves from external ultrasonic transducers, is located within the flow channel. Laminar flow is maintained in the flow channel. Blood cells and platelets are separated from blood plasma or blood serum at the end of the flow channel and collected. The method described herein allows fluid components to differentially migrate to areas of preferred acoustic interaction. The parameters that affect separation of particles are size, density, compressibility of the particles, and the fluid surrounding the particles.

What is claimed is: 
     
       1. A method for removing particles from a sample of fluid comprising a particulate component suspended in a liquid component, said method comprising:
 providing a sample of fluid; 
 introducing the sample of fluid into an apparatus, the apparatus comprising:
 a flow channel defined by a first layer and a second layer, the flow channel comprising:
 a first section having a first width; 
 a second section having a cross section that increases to a second width, then decreases to a third width; and 
 a third section having the third width, a first end of the second section coupled to the first section and a second end of the second section coupled to the third section; 
 
 an inlet channel extending through one of the first layer or the second layer and coupled to the first section; 
 a first outlet channel extending through one of the first layer or the second layer and coupled to the second section; and 
 a second outlet channel extending through one of the first layer or the second layer and coupled to the third section; 
 
 providing an acoustic field within the flow channel, which field contains acoustic standing waves generated by external ultrasonic transducers; 
 maintaining a laminar flow of the sample of fluid in the flow channel; 
 removing near field acoustic effects; 
 separating the particulate component from the liquid component; and 
 collecting the liquid component. 
 
     
     
       2. The method of  claim 1  further comprising manipulating the particulate component with the acoustic standing waves generated by the ultrasonic transducers without contacting the particulate component. 
     
     
       3. The method of  claim 1 , wherein the acoustic standing waves maintain acoustic nodes and antinodes in different layers of the flow of the sample of fluid. 
     
     
       4. The method of  claim 1 , wherein the particulate component and the liquid component migrate differentially to areas of preferred acoustic interaction. 
     
     
       5. The method of  claim 1 , wherein the particulate component comprises blood cells and the liquid component comprises at least one of blood plasma or blood serum, and wherein at least one of a size, a density or a compressibility of the blood cells or the at least one of blood plasma or blood serum affect the separation of the blood cells from the at least one of blood plasma or blood serum. 
     
     
       6. The method of  claim 1  further comprising constructing the flow channel to enable the laminar flow of the sample of fluid. 
     
     
       7. The method of  claim 1 , wherein the first layer and second layer are parallel or substantially parallel and form walls of the flow channel. 
     
     
       8. The method of  claim 7 , wherein the walls are separated a distance greater than about 1000 μm and a length of the flow channel is greater than about 30 mm. 
     
     
       9. The method of  claim 1 , wherein removing unstable near field acoustic effect comprises use of a delay line. 
     
     
       10. The method of  claim 9 , wherein the transducers and the delay line are attached to the flow channel to cause an incident angle of the wave relative to the wall to be approximately 45°. 
     
     
       11. The method of  claim 1 , wherein at least one of the first layer or the second layer of the flow channel is a delay channel. 
     
     
       12. The method of  claim 11 , wherein collecting the liquid component comprises removing the liquid component via the first outlet channel of the flow channel. 
     
     
       13. The method of  claim 1  further comprising using refraction and reflection of sound waves and the standing waves with nodes at a center of the flow channel for one or more of providing the acoustic field, maintaining the laminar flow or separating the particulate component from the liquid component. 
     
     
       14. The method of  claim 1  further comprising concentrating the particulate component in a central zone of the flow channel, wherein the particulate component comprises blood cells. 
     
     
       15. The method of  claim 1  further comprising expanding a width of the flow channel, at a collection zone to maintain laminar flow and to avoid turbulence. 
     
     
       16. The method of  claim 1  further comprising performing in vitro diagnostic analysis using the liquid component, wherein the liquid component comprises at least one of blood plasma or blood serum. 
     
     
       17. The method of  claim 1  further comprising aligning the particulate component along one or more light paths using flow cytometry, wherein the particulate component comprises cells. 
     
     
       18. The method of  claim 1 , wherein the sample of fluid is whole blood, the particulate component comprises blood cells, and the liquid component comprises at least one of blood plasma or blood serum. 
     
     
       19. The method of  claim 1 , wherein introducing the sample of fluid comprises introducing the sample of fluid into an inlet port of the inlet channel. 
     
     
       20. The method of  claim 1 , wherein collecting the liquid component comprises removing the liquid component via the first outlet channel and an outlet port of the first outlet channel. 
     
     
       21. The method of  claim 1  further comprising collecting the particulate component. 
     
     
       22. The method of  claim 21 , wherein the particulate component is collected at a first location and the liquid component is collected at a second location different than the first location. 
     
     
       23. The method of  claim 22  further comprising adjusting one or more of a width of the flow channel or a wavelength of at least one of the transducers to change at least one of the first location or the second location. 
     
     
       24. The method of  claim 1 , wherein each of the transducers has triangular cross-sectional area. 
     
     
       25. The method of  claim 1  further comprising introducing a buffer into the flow channel. 
     
     
       26. The method of  claim 25 , wherein the buffer comprises phosphate buffered saline. 
     
     
       27. The method of  claim 1  further comprising adjusting a wavelength of one or more of the transducers based on a width of the flow channel. 
     
     
       28. The method of  claim 27 , wherein the width is one half the wavelength. 
     
     
       29. The method of  claim 1 , wherein the apparatus further comprises a third outlet channel coupled to the second section. 
     
     
       30. The method of  claim 29 , wherein the first outlet channel is positioned opposite the flow channel from the third outlet channel. 
     
     
       31. The method of  claim 29 , wherein collecting the liquid component comprises removing the liquid component via the first outlet channel and the third outlet channel. 
     
     
       32. The method of  claim 31  further comprising collecting the particulate component via the second outlet channel. 
     
     
       33. The method of  claim 1 , the second outlet to collect the particulate component. 
     
     
       34. The method of  claim 1 , wherein the laminar flow causes the particulate component to flow in a forward direction through the first, second and third sections of the flow channel. 
     
     
       35. A method comprising:
 providing an acoustic field within a flow channel, the field comprising acoustic standing waves; 
 maintaining a laminar flow of a sample of fluid in the flow channel, the flow channel defined by a first side wall and a second side wall opposite the first side wall, the sample comprising a particulate component suspended in a liquid component; 
 separating the particulate component from the liquid component using an outlet port that extends through the first sidewall and into the flow channel, a portion of the outlet port axially aligned with the flow channel; and 
 collecting the liquid component.